Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications.

Zsuzsa Szondy,Gregory J Tsay,Zsolt Sarang,Ã‰Va Garabuczi,Gergely Joã³S

doi:10.3389/fimmu.2014.00354

Abstract

In healthy individuals, billions of cells die by apoptosis every day. Removal of the dead cells by phagocytosis (a process called efferocytosis) must be efficient to prevent secondary necrosis and the consequent release of pro-inflammatory cell contents that damages the tissue environment and provokes autoimmunity. In addition, detection and removal of apoptotic cells generally induces an anti-inflammatory response. As a consequence improper clearance of apoptotic cells, being the result of either genetic anomalies and/or a persistent disease state, contributes to the establishment and progression of a number of human chronic inflammatory diseases such as autoimmune and neurological disorders, inflammatory lung diseases, obesity, type 2 diabetes, or atherosclerosis. During the past decade, our knowledge about the mechanism of efferocytosis has significantly increased, providing therapeutic targets through which impaired phagocytosis of apoptotic cells and the consequent inflammation could be influenced in these diseases.

Highlights

Efficient execution of apoptotic cell death followed by efficient clearance mediated by professional and by non-professional neighboring phagocytes, is a key mechanism in maintaining tissue homeostasis
AFFECTING RECOGNITION AND BINDING OF APOPTOTIC CELLS If lack of sufficient milk-fat globulin-E8 (MFG-E8) production leading to improper efferocytosis participates in the pathomechanism of a disease, providing MFG-E8 in recombinant protein form to the site of acute inflammation might enhance the efficiency of efferocytosis
It is worth noting that we found daidzein, which is a plant-derived diphenolic isoflavone present in a number of plants and herbs [89] and has liver X receptor (LXR) and PPARγ activating activity [90], to enhance efferocytosis efficiently

Summary

Introduction

Efficient execution of apoptotic cell death followed by efficient clearance mediated by professional and by non-professional neighboring phagocytes, is a key mechanism in maintaining tissue homeostasis. Increasing evidence suggest that improper clearance of apoptotic cells, being the result of either genetic anomalies and/or a persistent disease state, contributes to the establishment and progression of a number of human diseases via affects on the maintenance of tissue homeostasis, tissue repair, and inflammation [6].

Results

Conclusion